Search results for "PROTEIN INTERACTIONS"

Editorial: The Role of Protein Post-Translational Modifications in Protein-RNA Interactions and RNP Assemblies

2022

The Protein Structure Context of PolyQ Regions.

2016

Proteins containing glutamine repeats (polyQ) are known to be structurally unstable. Abnormal expansion of polyQ in some proteins exceeding a certain threshold leads to neurodegenerative disease, a symptom of which are protein aggregates. This has led to extensive research of the structure of polyQ stretches. However, the accumulation of contradictory results suggests that protein context might be of importance. Here we aimed to evaluate the structural context of polyQ regions in proteins by analysing the secondary structure of polyQ proteins and their homologs. The results revealed that the secondary structure in polyQ vicinity is predominantly random coil or helix. Importantly, the region…

Carnosine Inhibits Aβ42Aggregation by Perturbing the H-Bond Network in and around the Central Hydrophobic Cluster

2013

Aggregation of the amyloid-β peptide (Aβ) into fibrillar structures is a hallmark of Alzheimer's disease. Thus, preventing self-assembly of the Aβ peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aβ aggregation. Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of Aβ42 but nonetheless inhibits amyloid growth. Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric Aβ42 by salt bridges with charge…

Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity

2012

Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe…

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

2020

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. Herein, we present a computational study aimed at identifying small molecules potentially able to target RBD. Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV…

Molecular signatures of silencing suppression degeneracy from a complex RNA virus

2021

As genomic architectures become more complex, they begin to accumulate degenerate and redundant elements. However, analyses of the molecular mechanisms underlying these genetic architecture features remain scarce, especially in compact but sufficiently complex genomes. In the present study, we followed a proteomic approach together with a computational network analysis to reveal molecular signatures of protein function degeneracy from a plant virus (as virus-host protein-protein interactions). We employed affinity purification coupled to mass spectrometry to detect several host factors interacting with two proteins of Citrus tristeza virus (p20 and p25) that are known to function as RNA sil…

MIPPIE: the mouse integrated protein–protein interaction reference

2020

Abstract Cells operate and react to environmental signals thanks to a complex network of protein–protein interactions (PPIs), the malfunction of which can severely disrupt cellular homeostasis. As a result, mapping and analyzing protein networks are key to advancing our understanding of biological processes and diseases. An invaluable part of these endeavors has been the house mouse (Mus musculus), the mammalian model organism par excellence, which has provided insights into human biology and disorders. The importance of investigating PPI networks in the context of mouse prompted us to develop the Mouse Integrated Protein–Protein Interaction rEference (MIPPIE). MIPPIE inherits a robust infr…

Synthesis and biological evaluation of some new 2-phenylpropiolamidobenzamides as potential antagonists of the HDM2-p53 protein-protein interactions

2009

A Protein-Interaction Array Inside a Living Cell

2013

Cell phenotype is determined by protein network states that are maintained by the dynamics of multiple protein interactions.1 Fluorescence microscopy approaches that measure protein interactions in individual cells, such as by Forster resonant energy transfer (FRET), are limited by the spectral separation of fluorophores and thus are most suitable to analyze a single protein interaction in a given cell. However, analysis of correlations between multiple protein interactions is required to uncover the interdependence of protein reactions in dynamic signal networks. Available protein-array technologies enable the parallel analysis of interacting proteins from cell extracts, however, they can …

Repurposing of Drugs Targeting YAP-TEAD Functions

2018

Drug repurposing is a fast and consolidated approach for the research of new active compounds bypassing the long streamline of the drug discovery process. Several drugs in clinical practice have been reported for modulating the major Hippo pathway’s terminal effectors, namely YAP (Yes1-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif) and TEAD (transcriptional enhanced associate domains), which are directly involved in the regulation of cell growth and tissue homeostasis. Since this pathway is known to have many cross-talking phenomena with cell signaling pathways, many efforts have been made to understand its importance in oncology. Moreover, this could be rele…